Mania following subthalamic nucleus (STN) deep brain stimulation (DBS) is well described and obvious to both the patient and their physician. The authors describe two patients who developed hypomania following STN-DBS but were unaware of their mood disturbance. Two Parkinson's patients with no previous mood disorders received bilateral STN electrodes. Both experienced dramatic improvement in their motor function and neither complained of any side effects. Their families reported detrimental hypomanic behaviour. Readjusting the stimulation parameters resolved the hypomania with continued motor benefits. The authors draw attention to potential adverse effects of STN-DBS that might be neglected by patients.

Parkinson's disease (PD) is among the disorders in which the placebo effect can play a significant role. [1][2][3][4] Functional imaging studies have demonstrated that this effect is related to dopamine release in the striatum. 5 This dopamine release appears to be linked to expectation of reward (i.e., clinical benefit), which is in turn mediated by dopamine release in the ventral striatum.Since the initial description of high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the treatment of severe PD in 1995, 6 many centers have reported efficacy and the safety of this procedure. 7-10 Despite its clinical success, the mechanism underlying the effects of STN DBS in PD remains unknown. 11 Only two previous studies have been published describing the role played by expectation in the outcome of movement velocity in parkinsonian patients treated with effective STN DBS. 12,13 The objective of this study is to determine whether the degree to which patients with Parkinson's disease expect therapeutic benefit from STN DBS influences the magnitude of their improved motor response. PATIENTS AND METHODS This study was approved by the University of British Columbia Clinical Research Ethics Board (C98-0404).Ten patients with idiopathic Parkinson's disease who had received bilateral STN DBS were enrolled in the study. Disabling motor fluctuations with severe bradykinesia and dyskinesias secondary to the chronic use of antiparkinsonian medication were the main indications for surgery. There were two women and eight men whose mean age was 61 years (range, 42-78 years). The mean duration of the symptoms before surgery was 14 years (range, 6 -23 years). All underwent microelectrode-guided placement of bilateral deep brain stimulation electrodes (model 3389; Medtronic, Minneapolis, MN) in the subthalamic nuclei, connected to an implantable pulse generator below the left clavicle (Kinetra, model 7428; Medtronic). The stimulation parameters and reduced level of medications were then optimized over several months. At the moment of the study, the mean dose of L-dopa and dopamine agonist in the form of L-dopa equivalents that the patients were receiving was 690 mg (range, 200 -1,300 mg). Patients were then tested for this study after a 12-hour period of no antiparkinsonian medications and no stimulation. Four consecutive Unified Parkinson's Disease Rating Scale (UPDRS) scores were performed in the following conditions: stimulator OFF and patient aware that the stimulation was OFF; stimulator OFF and patient unaware whether the stimulation was ON or OFF; stimulator ON, patient aware; stimulator ON, patient blind. The four conditions were randomly assigned. The stimulator remained OFF or was switched OFF for 10 minutes after each evaluation. The patients were evalu-

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IntroductionWe investigated the status of estrogen receptor alpha (ERα), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) in primary tumor and in the corresponding brain metastases in a consecutive series of breast cancer patients. Additionally, we studied factors potentially influencing conversion and evaluated its association with survival.MethodsThe study group included 120 breast cancer patients. ERα, PR, and HER2 status in primary tumors and in matched brain metastases was determined centrally by immunohistochemistry and/or fluorescence in situ hybridization.ResultsUsing the Allred score of ≥ 3 as a threshold, conversion of ERα and PR in brain metastases occurred in 29% of cases for both receptors, mostly from positive to negative. Conversion of HER2 occurred in 14% of patients and was more balanced either way. Time to brain relapse and the use of chemotherapy or trastuzumab did not influence conversion, whereas endocrine therapy induced conversion of ERα (P = 0.021) and PR (P = 0.001), mainly towards their loss. Receptor conversion had no significant impact on survival.ConclusionsReceptor conversion, particularly loss of hormone receptors, is a common event in brain metastases from breast cancer, and endocrine therapy may increase its incidence. Receptor conversion does not significantly affect survival.

BackgroundA better understanding of immune response in breast cancer brain metastases (BCBM) may prompt new preventive and therapeutic strategies.MethodsImmunohistochemical expression of stromal tumor-infiltrating lymphocytes (TILs: CD4, CD8, CTLA4), macrophage/microglial cells (CD68), programmed cell death protein 1 receptor (PD-1), programmed cell death protein 1 receptor ligand (PD-L)1, PD-L2 and glial fibrillary acid protein was assessed in 84 BCBM and their microenvironment.ResultsMedian survival after BCBM excision was 18.3 months (range 0–99). Median number of CD4+, CD8+ TILs and CD68+ was 49, 69 and 76 per 1 mm2, respectively. PD-L1 and PD-L2 expression in BCBM was present in 53 % and 36 % of cases, and was not related to BCBM phenotype. PD-1 expression on TILs correlated positively with CD4+ and CD8+ TILs (r = 0.26 and 0.33), and so did CD68+ (r = 0.23 and 0.27, respectively). In the multivariate analysis, survival after BCBM excision positively correlated with PD-1 expression on TILs (hazard ratio (HR) = 0.3, P = 0.003), CD68+ infiltration (HR = 0.2, P < 0.001), brain radiotherapy (HR = 0.1, P < 0.001), endocrine therapy (HR = 0.1, P < 0.001), and negatively with hormone-receptor-negative/human epidermal growth factor receptor 2 (HER2)-positive phenotype of primary tumor (HR = 2.6, P = 0.01), HER2 expression in BCBM (HR = 4.9, P = 0.01).ConclusionsPD-L1 and PD-L2 expression is a common occurrence in BCBM, irrespective of primary tumor and BCBM phenotype. Favorable prognostic impact of PD-1 expression on TILs suggests a beneficial effect of preexisting immunity and implies a potential therapeutic role of immune checkpoint inhibitors in BCBM.

Stereotactic technique and the introduction of deep brain stimulation (DBS) can be considered two milestones in the field of surgical neuromodulation. At present the role of DBS in the treatment of clinically and epidemiologically relevant movement disorders is widely accepted and DBS procedures are performed in many clinical centers worldwide. Here we review the current state of the art of DBS treatment for the most common movement disorders: Parkinson’s disease, essential tremor, and dystonia. In this review, we give a brief description of the candidate patient selection criteria, the different anatomical targets for each of these condition, and the expected outcomes as well as possible side effects.

BARD1 and RAD51 are frequently overexpressed in brain metastases from breast cancer and may constitute a mechanism to overcome reactive oxygen species-mediated genotoxic stress in the metastatic brain.

Background: Microlesion effect (MLE) is a commonly observed phenomenon after electrode insertion into the subthalamic nucleus (STN) for deep brain stimulation (DBS). Objectives: The aim of this study was to determine the presence of the MLE in the early postoperative period and the relationship between MLE and STN DBS. Methods: 74 patients with Parkinson’s disease were included in this study. Motor symptoms were evaluated preoperatively, within 48 h after electrode implantation and at 6 months with United Parkinson’s Disease Rating Scale part III (UPDRS-III). According to the improvement level with MLE, all participants were stratified into three groups: (1) less than 20%; (2) 20–40%, and (3) more than 40% in OFF medication states. The degree of improvement in UPDRS-III with DBS ON for each MLE group was assessed at the 6-month follow-up. Regression analysis was applied for the evaluation of the relationship between MLE and improvement with DBS ON. Results: Mean results in UPDRS-III with the MLE in ON and OFF medication states were 22.1 ± 10.5 and 42.1 ± 14 points, respectively. At the 6-month follow-up, with active stimulation, results tended to further ameliorate to 14.6 (59.4%) points in ON and 20.8 (55.3%) in OFF. Mean improvement in MLE groups were: 33.6% group 1, 47.5% group 2 and 61.4% group 3. Regression analysis revealed a positive correlation between the MLE and results at 6 months with DBS ON. Conclusion: Results proved the presence of MLE in the early postoperative period. Furthermore, a positive correlation between MLE and improvement degree with active stimulation was observed.